Abstract

1109

Hodgkin lymphoma in young adults is thought to be caused in part by late exposure to a common childhood virus. Genetic factors are also important since identical twins of cases have a much greater risk than fraternal twins of cases. We previously demonstrated that IL-6 levels are 68% higher in unafffected identical twins of young adult Hodgkin lymphoma cases (surrogate cases) compared to matched controls. Further, we showed that an IL-6 genotype (-174 CC) associated with lower IL-6 levels was protective against Hodgkin lymphoma. IL-10 has also been correlated to the prognosis of young adult Hodgkin lymphoma and is elevated in untreated cases. In the same set of cases, of young adult Hodgkin lymphoma (n=71), their unaffected identical twins (n=50), and their matched controls (n= 71), we measured IL-10 levels in supernatant from cultured PBMCs using ELISA assays. After log transformation, IL-10 levels in unaffected identical twins of cases (surrogate cases, n= 50) were compared to their matched controls using an analysis of covariance adjusting for ELISA plate, age and gender. Surrogate cases (unaffected twins) had IL-10 levels that were 18.6% lower compared to controls (-26.8 pg/ml; p=0.21). IL-10 genotypes of the -819 and -1082 SNPs were evaluated in the 71 cases and matched controls using allele-specific PCR. The -819 SNP was not related to the risk of young adult Hodgkin lymphoma in cases compared to controls (p for increasing number of T alleles = 0.92). However, carriers of the -1082 GG genotype were 46% less likely to develop young adult Hodgkin lymphoma compared to carriers of the AA genotype (OR for GG vs. AA = 0.54, 95% CL =0.21-1.39; OR for GA vs. AA = 0.74, 95% CL=0.30-1.83). Increasing numbers of G alleles were significantly associated with a decreased risk of the disease (p=0.03 for linear trend) among the 44 identical twin cases and their matched controls. In summary, our results suggest that the GG genotype of the -1082 IL-10 SNP, associated with higher IL-10 levels in some studies, may protect against young adult Hodgkin lymphoma. The relationship between other IL-10 SNPs and Hodgkin lymphoma should also be examined and haplotype analyses performed to clarify the association.